Serum IgG Profiling of Toddlers Reveals a Subgroup with Elevated Seropositive Antibodies to Viruses Correlating with Increased Vaccine and Autoantigen Responses

Purpose

The human antibody repertoire forms in response to infections, the microbiome, vaccinations, and environmental exposures. The specificity of such antibody responses was compared among a cohort of toddlers to identify differences between seropositive versus seronegative responses.

Methods

An assessment of the serum IgM and IgG antibody reactivities in 197 toddlers of 1- and 2-years of age was performed with a microfluidic array containing 110 distinct antigens. Longitudinal profiling was done from years 1 to 2. Seropositivity to RNA and DNA viruses; bacteria; live attenuated, inactive, and subunit vaccines; and autoantigens was compared. A stratification was developed based on quantitative variations in the IgG responses. Clinical presentations and previously known genetic risk alleles for various immune system conditions were investigated in relation to IgG responses.

Results

IgG reactivities stratified toddlers into low, moderate, and high responder groups. The high group (17%) had elevated IgG responses to multiple RNA and DNA viruses (e.g., respiratory syncytial virus, Epstein-Barr virus, adenovirus, Coxsackievirus) and this correlated with increased responses to live attenuated viral vaccines and certain autoantigens. This high group was more likely to be associated with gestational diabetes and an older age. Genetic analyses identified polymorphisms in the IL2RB, TNFSF4, and INS genes in two high responder individuals that were associated with their elevated cytokine levels and clinical history of eczema and asthma.

Conclusion

Serum IgG profiling of toddlers reveals correlations between the magnitude of the antibody responses towards viruses, live attenuated vaccines, and certain autoantigens. A low responder group had much weaker responses overall, including against vaccines. The serum antibody screen also identifies individuals with IgG responses to less common infections (West Nile virus, parvovirus, tuberculosis). The characterization of the antibody responses in combination with the identification of genetic risk alleles provides an opportunity to identify children with increased risk of clinical disease.

     

Left Main Coronary Artery Thrombosis With Acute Myocardial Infarction: A Management Dilemma

Left main coronary artery (LMCA) thrombosis with acute myocardial infarction is a rare condition with very high mortality. The low incidence of this condition and exclusion of patients with LMCA thrombosis from clinical trials prevent the development of optimal management strategy in these patients. Therefore, there are no clear-cut guidelines describing an evidence-based approach for this condition. We describe a patient with LMCA thrombosis presenting with acute myocardial infarction, who was found to have hypercoagulable state related to homocysteinemia on further work-up. This case highlights the challenges faced during the management of this rare condition due to lack of clear-cut guidelines describing an evidence-based approach.     

In vitro antibacterial potential of metal oxide nanoparticles against antibiotic resistant bacterial pathogens

ObjectiveTo investigate the antibacterial potential of 5 different metal oxide nanoparticles against antibiotic resistant bacterial pathogens viz., Pseudomonas aeruginosa, Klebsiella sp. Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus sp.MethodsThe antibacterial activity of the five different nanoparticles was assessed by well diffusion method. Different concentrations of the nanoparticles were analyzed by MIC and MBC techniques. Finally the potential MgO nanoparticle was also subjected for the time kill assay method.ResultsThe results reveal that, the MgO nanoparticle showed maximum sensitivity [(16.00±0.53) mm dia] against Streptococcus pneumoniae and showed minimum sensitivity against Klebsiella sp. [(9.00±0.31) mm dia]. None of the nanoparticles showed sensitivity against the Streptococcus sp. The MIC result reveals that, the MgO nanoparticle showed maximum inhibition at a concentration of 10 μ g against Streptococcus pneumoniae. Moreover, the time kill assay reveals that, the bacterial growth was inhibited from the 2nd h onwards at a concentration of 10μ g.ConclusionsIt is concluded from the present findings that, the MgO nanoparticle could be used as an alternative antibacterial agent after completing successful in vivo trials.     

The Story of the Texas Pain Society: Formation and Function of a Regional Pain Society

Abstract: The idea of forming a Texas Pain Society came to the Founders in 1987 due to disparity and deficiencies in the practice of pain management in the United States and, in particular, the State of Texas. The Founders considered very carefully the implication of forming such a society. They diligently mapped out the mission and goals of the Texas Pain Society in those early formative years. This report is the history of Texas Pain Society as the activities unfolded from 1989 to 2011. The reader may question why there is a need to tell such a story. We believe strongly that, with disparities of standards of practice in pain medicine and poor recognition of advances in pain management, this scenario is quite common in many states and countries. The practitioners of pain management in these regions certainly must have considered getting together and forming a consensus on the standards of practice in their communities. This historical report of the Texas Pain Society provides the relevant information necessary and the efforts to be made for a society’s mission to achieve its goals and have an ongoing impact in its own region. We hope that we have shed some light on a process for the formation of a regional pain society such as ours. ?     

Chronic α1-Na/K-ATPase inhibition reverses the elongation of the axon initial segment of the hippocampal CA1 pyramidal neurons in Angelman syndrome model mice

Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of the maternal UBE3A gene. The hippocampus is one of the most prominently affected brain regions in AS model mice, manifesting in severe hippocampal-dependent memory and plasticity deficits. Previous studies in AS mice reported an elongated axon initial segment (AIS) in pyramidal neurons (PNs) of the hippocampal CA1 region. These were the first reports in mammals to show AIS elongation in vivo. Correspondingly, this AIS elongation was linked to enhanced expression of the α1 subunit of Na⁺/K⁺-ATPase (α1-NaKA). Recently, it was shown that selective pharmacological inhibition of α1-NaKA by marinobufagenin (MBG) in adult AS mice rescued the hippocampal-dependent deficits via normalizing their compromised activity-dependent calcium (Ca⁺²) dynamics. In the herein study, we showed that a chronic selective α1-NaKA inhibition reversed the AIS elongation in hippocampal CA1 PNs of adult AS mice, and differentially altered their excitability and intrinsic properties. Taken together, our study is the first to demonstrate in vivo structural plasticity of the AIS in a mammalian model, and further elaborates on the modulatory effects of elevated α1-NaKA levels in the hippocampus of AS mice.Subject terms: Cellular neuroscience, Autism spectrum disorders, Developmental disorders     

The distal radio-ulnar joint

The distal radio-ulnar joint can be a source of ulnar-sided wrist pain. The complex anatomy in this region of the wrist can make diagnosis of distal radio-ulnar joint problems challenging. An understanding of the anatomy can aid an accurate diagnosis. An overview of the anatomy, biomechanics and conditions of the distal radio-ulnar joint is provided, together with other common causes of ulnar-sided wrist pain.